# This Week in Science

Science  28 Feb 2020:
Vol. 367, Issue 6481, pp. 995
1. Plant Science

# Wavy walls built by nanofilaments

1. Pamela J. Hines

In the model plant Arabidopsis, pavement cells fit together with the lobes and curves of jigsaw puzzle pieces. Such complex cell shapes, in plants, were generally thought to be driven by turgor pressure. Haas et al. now show that the extracellular cell wall can actively shape the cell it contains without relying on turgor pressure. Nanofilaments of pectin homogalacturonan in the cell wall shift between crystalline and anisotropic phases according to whether they are methylated. The shift in form drives changes in cell wall shape that stand independent of turgor pressure.

Science, this issue p. 1003

2. Neuroscience

# Speech versus music in the brain

1. Peter Stern

To what extent does the perception of speech and music depend on different mechanisms in the human brain? What is the anatomical basis underlying this specialization? Albouy et al. created a corpus of a cappella songs that contain both speech (semantic) and music (melodic) information and degraded each stimulus selectively in either the temporal or spectral domain. Degradation of temporal information impaired speech recognition but not melody recognition, whereas degradation of spectral information impaired melody recognition but not speech recognition. Brain scanning revealed a right-left asymmetry for speech and music. Classification of speech content occurred exclusively in the left auditory cortex, whereas classification of melodic content occurred only in the right auditory cortex.

Science, this issue p. 1043

3. Ecological Speciation

# Resisting extinction

1. Sacha Vignieri

Prevailing evolutionary wisdom tells us that ecological differentiation leads to speciation. Whether this pattern can be seen over paleontological time, however, has been difficult to test. Knope et al. looked at a dataset of thousands of modern and extinct marine groups and found the relationship to be more complex than expected. Ecological diversification is associated with lower rates of origination, and the taxonomical richness seemingly associated with these groups is due to resistance to extinction. Furthermore, the researchers found that the strong association between ecological differentiation and taxonomic diversity is a recent development shaped by extinction events over time.

Science, this issue p. 1035

4. Fluid Dynamics

# Machine-learning fluid flow

1. Jelena Stajic

Quantifying fluid flow is relevant to disciplines ranging from geophysics to medicine. Flow can be experimentally visualized using, for example, smoke or contrast agents, but extracting velocity and pressure fields from this information is tricky. Raissi et al. developed a machine-learning approach to tackle this problem. Their method exploits the knowledge of Navier-Stokes equations, which govern the dynamics of fluid flow in many scientifically relevant situations. The authors illustrate their approach using examples such as blood flow in an aneurysm.

Science, this issue p. 1026

5. Tumor Immunology

# Getting a hold on MDSCs

1. Anand Balasubramani

Myeloid-derived suppressor cells (MDSCs) are immune cells that mediate immune suppression and are correlated with progressing cancer. How these cells arise and whether they can be therapeutically targeted akin to exhausted T cells are areas of active investigation. A persistent challenge in studying MDSCs has been the identification of MDSC-specific cell-surface markers that can facilitate their isolation and characterization. Using single-cell RNA sequencing in a mouse model of breast cancer, Alshetaiwi et al. defined gene signatures that distinguish MDSCs from other myeloid and granulocytic cells. They identified the protein CD84 to be a robust cell-surface marker for identification of MDSCs in both human and murine breast cancer. Whether their findings can be extended to MDSCs in other cancer settings remains to be seen.

Sci. Immunol. 5, eaay6017 (2020).

6. Optics

# Ultrafast vortex microlasers

1. Ian S. Osborne

For applications in ultrafast communication, all-optical switches will require low energy consumption, high speed, a strong modulation ratio, a small footprint, and on-chip integration. Although the small footprint and on-chip integration are accessible, the trade-off between low energy consumption and high speed has been challenging. Huang et al. exploited the idea of bound states in the continuum, effectively a high–quality (Q) cavity without the physical cavity, to design vortex lasers with highly directional output and single-mode operation. With the trade-off between low energy consumption and high speed now broken, it should be possible to realize ultrafast optical switching that meets all the requirements of modern classic and quantum information.

Science, this issue p. 1018

7. Social Science

# Economic losses from illicit fish trade

1. Jeremy Jackson

Illegal, unreported, and unregulated fishing—and the subsequent illicit fish trade market that follows—have a substantial impact on local and national economies. Sumaila et al. estimate that the illicit trade in marine fish catch adds up to between 8 million and 14 million metric tons per year. With suggested gross revenues totaling $9 billion to$17 billion, the researchers estimate potential losses of $26 billion to$50 billion to world economies owing to the diversion of fish from the legitimate trade system. Bold policy and action by both the private and public sectors are needed to mitigate the substantial economic effects of illicit trade in marine fish catch.

8. Organic Chemistry

# Amines as a gateway to alkyl radicals

1. Jake Yeston

In recent years, photoredox catalysis driven by blue light has often been used to oxidize carbon centers adjacent to nitrogen. Constantin et al. now show that these aminoalkyl radicals can, in turn, conveniently strip iodine atoms from a variety of alkyl carbons. The new alkyl radicals that result readily undergo deuteration and couplings such as alkylation, allylation, and olefination. The upshot is that simple amines can replace more hazardous conventional reagents such as trialkyltin compounds in the homolytic activation and functionalization of halocarbons.

Science, this issue p. 1021

9. Cancer

# Improving the drug development pipeline

1. Gemma Alderton

Artificial intelligence (AI) applications are being developed to improve cancer drug discovery and administration. Moreover, AI can improve clinical trial design and therapeutic dosing strategies such as adaptive therapy, whereby patients are treated according to tumor response to avoid resistance. In a Perspective, Ho discusses how AI applications can improve cancer drug development and the challenges to be overcome.

Science, this issue p. 982

10. Clinical Trials

# CRISPR takes first steps in humans

1. Priscilla N. Kelly

CRISPR-Cas9 is a revolutionary gene-editing technology that offers the potential to treat diseases such as cancer, but the effects of CRISPR in patients are currently unknown. Stadtmauer et al. report a phase 1 clinical trial to assess the safety and feasibility of CRISPR-Cas9 gene editing in three patients with advanced cancer (see the Perspective by Hamilton and Doudna). They removed immune cells called T lymphocytes from patients and used CRISPR-Cas9 to disrupt three genes (TRAC, TRBC, and PDCD1) with the goal of improving antitumor immunity. A cancer-targeting transgene, NY-ESO-1, was also introduced to recognize tumors. The engineered cells were administered to patients and were well tolerated, with durable engraftment observed for the study duration. These encouraging observations pave the way for future trials to study CRISPR-engineered cancer immunotherapies.

11. Microbiota

# Mouse mothers transfer metabolic mode

1. Caroline Ash

Obesity and metabolic diseases tend to go together, and humans who become obese are also prone to type 2 diabetes and cardiovascular problems. Starting with the observation that offspring of germ-free mice tended to become obese on high-fat diets, Kimura et al. investigated how the presence of the microbiota might be protective in mice (see the Perspective by Ferguson). Short-chain fatty acids (SCFAs) from the microbiota are known to suppress insulin signaling and reduce fat deposition in adipocytes. Further experiments showed that SCFAs in the bloodstream were able to pass from a non–germ-free mother's gut microbiota across the placenta and into the developing embryos. The authors found that in the embryos, the SCFA propionate mediates not only insulin levels through GPR43 signaling but also sympathetic nervous system development through GPR41 signaling. A high-fiber diet promoted propionate production from the maternal microbiota, and maternal antibiotic treatment resulted in obese-prone offspring.

12. Immunology

# Hefty structures of IgA and IgM complexes

1. Seth Thomas Scanlon

Immunoglobulin M (IgM) and IgA are antibody isotypes that can form higher-order secretory complexes (sIgM and sIgA), which allows them to effectively bind and neutralize antigens with low-affinity repetitive epitopes, such as those found on the surface of many bacteria and viruses. The assembly and transport of these molecules is also dependent on the joining chain (J-chain) and the polymeric immunoglobulin receptor (pIgR) secretory component (SC). The architecture of these complex, multimeric structures has remained elusive. Li et al. resolved cryo–electron microscopy structures of the sIgM-Fc pentamer in complex with the J-chain and SC. Using similar techniques, Kumar et al. visualized dimeric, tetrameric, and pentameric structures of secretory sIgA-Fc interacting with the J-chain and SC. Both groups report highly similar mechanisms wherein the J-chain serves as a template for antibody oligomerization. An unanticipated, amyloid-like assembly of the oligomerized structure is present in both cases, with the J-chain conferring asymmetry for pIgR binding and transcytosis. These studies may inform structure-based engineering of these molecules for future therapeutic purposes.

Science, this issue p. 1014, p. 1008

13. Batteries

# Metastable pathways allow high rates

1. Marc S. Lavine

In batteries that allow for fast charging and discharging, lithium usually forms a solid solution with the anode so that the only limiting factor is the ionic diffusion. However, for a lithium titanate (Li4Ti5O12) anode, the lithium ions interact with two phases and the diffusion is slow in both, but it still shows high-rate capabilities. Zhang et al. used electron energy-loss spectroscopy combined with density functional theory calculations to probe the anomalous behavior. They found that a diffuse interface forms between the starting and ending compositions, Li4Ti5O12 and Li7Ti5O12, and this is what allows the lithium ions to travel quickly.

Science, this issue p. 1030

14. Cell Biology

# Polymerization regulates hexokinase activity

1. Stella M. Hurtley

The yeast hexokinase Glk1 is an actin-fold protein that forms polymers in response to binding its substrates and products. Stoddard et al. now show that Glk1 polymers are structurally distinct from actin filaments and suggest that polymerization of Glk1 evolved independently of the polymerization of other actin-like polymers. Glk1 polymerization inhibits its hexokinase activity, and the monomerpolymer equilibrium appears to set a maximum rate for the entire enzyme pool rather than a maximum rate per enzyme. This inhibition was found to be important for cell viability in the context of nutrient shifts, allowing yeast cells to modulate their metabolism rapidly in response to stochastic changes in the environment.

Science, this issue p. 1039

15. Prenatal Therapies

# When treating at birth is too late

1. Yevgeniya Nusinovich

Mucopolysaccharidosis type VII (MPS7) is a rare and severe lysosomal storage disorder that causes dysfunction of multiple organs, including the brain. By the time of birth, the organ damage may already be severe and the fetus may not survive. Thus, the prenatal period provides the most promising opportunity for intervention. Nguyen et al. assessed two prenatal approaches—in utero enzyme replacement therapy and in utero hematopoietic stem cell transplantation—and demonstrated the potential of these treatments to improve survival and functional outcomes in a mouse model of MPS7.

Sci. Transl. Med. 12, eaay8980 (2020).

16. Cell Biology

# Oriented mechanically, not by adhesion

1. Annalisa M. VanHook

Adherent cells position their spindle poles parallel to the plane of the substrate and orient the spindle within that plane according to cell shape–dependent mechanical forces. Anastasiou et al. found that proper spindle positioning in cultured cells was supported by integrin-mediated cell–extracellular matrix adhesion. Adhesion-dependent integrin activation was not required to position spindles parallel to the substrate plane, but force-dependent integrin activation was required to orient spindles in response to mechanical cues generated by adhesion topology.

Sci. Signal. 13, eaax9940 (2020).

17. Outer Solar System

# Examining Arrokoth

1. Keith T. Smith

The New Horizons spacecraft flew past the Kuiper Belt object (486958) Arrokoth (also known as 2014 MU69) in January 2019. Because of the great distance to the outer Solar System and limited bandwidth, it will take until late 2020 to downlink all the spacecraft's observations back to Earth. Three papers in this issue analyze recently downlinked data, including the highest-resolution images taken during the encounter (see the Perspective by Jewitt). Spencer et al. examined Arrokoth's geology and geophysics using stereo imaging, dated the surface using impact craters, and produced a geomorphological map. Grundy et al. investigated the composition of the surface using color imaging and spectroscopic data and assessed Arrokoth's thermal emission using microwave radiometry. McKinnon et al. used simulations to determine how Arrokoth formed: Two gravitationally bound objects gently spiraled together during the formation of the Solar System. Together, these papers determine the age, composition, and formation process of the most pristine object yet visited by a spacecraft.

Science, this issue p. eaay3999, p. eaay3705 , p. eaay6620; see also p. 980